Our goal is to provide accurate, object-independent estimates of contrast-agent concentration using energy- resolved CT. Energy-resolved CT has the potential to reduce the contrast dose and radiation dose of CT angiography exams. Combining energy-resolved CT with targeted K-edge contrast agents facilitates quantitative molecular CT, with the potential for improved spatial resolution (sub-mm), temporal resolution (sub-second) and quantitative accuracy (~5%) compared to nuclear medicine methods. Unlike conventional dual-kVp methods, energy-resolved CT distinguishes contrast materials by their distinct K-edge, enabling direct quantification. However, the accuracy and scan time of energy-resolved CT is currently limited by technological issues. This project develops innovative reconstruction and correction methods to overcome the limitations of energy-resolved CT, while increasing accuracy and reducing dose. This effort will enable faster translation of this beneficia technology into the clinic. We hypothesize that the proposed methods will quantify contrast-agent concentration to within 5% error with a one-second scan time. Specifically, the project will: (1) develop a practical spectral-response correction method, (2) develop region-of-interest material decomposition algorithms to reduce dose and pulse-pileup effects, and (3) develop a method for simultaneous estimation of contrast agent and scatter. The methods will be tested through phantom and animal experiments on our prototype energy-resolved CT system. Successful completion of the project will reduce radiation and contrast dose of CT angiography and provide important information about physiological function and disease states when combined with targeted tracers.